Reduction In Field Size Research Articles

Field size reduction enables Iso-NTCP escalation of tumor control probability for irradiation of lung tumors

Purpose: With the mean lung dose (MLD) as an estimator for the normal tissue complication probability (NTCP) of the lung, we assessed whether the probability of tumor control of lung tumors might be increased by dose escalation in combination with a reduction of field sizes, thus increasing target dose inhomogeneity while maintaining a constant MLD. Methods and Materials: An 8-MV AP-PA irradiation of a lung tumor, located in a cylindrically symmetric lung-equivalent phantom, was modeled using numerical simulation. Movement of the clinical target volume (CTV) due to patient breathing and setup errors was simulated. The probability of tumor control, expressed as the equivalent uniform dose (EUD) of the CTV, was assessed as a function of field size, under the constraint of a constant MLD. The approach was tested for a treatment of a non–small cell lung cancer (NSCLC) patient using the beam directions of the clinically applied treatment plan. Results: In the phantom simulation it was shown that by choosing field sizes that ensured a minimum dose of 95% in the CTV (“conventional” plan) taking into account setup errors and tumor motion, an EUD of the CTV of 43.8 Gy can be obtained for a prescribed dose of 44.2 Gy. By reducing the field size and thus shifting the 95% isodose surface inwards, the EUD increases to a maximum of 68.3 Gy with a minimum dose in the CTV of 55.2 Gy. This increase in EUD is caused by the fact that field size reduction enables escalation of the prescribed dose while maintaining a constant MLD. Further reduction of the field size results in decrease of the EUD because the minimum dose in the CTV becomes so low that it has a predominant effect on the EUD, despite further escalation of the prescribed dose. For the NSCLC patient, the EUD could be increased from an initial 62.2 Gy for the conventional plan, to 83.2 Gy at maximum. In this maximum, the prescribed dose is 88.1 Gy, and the minimum dose in the CTV is 67.4 Gy. In this case, the 95% isodose surface is conformed closely to the “static” CTV during treatment planning. Conclusions: Iso-NTCP escalation of the probability of tumor control is possible for lung tumors by reducing field sizes and allowing a larger dose inhomogeneity in the CTV. Optimum field sizes can be derived, having the highest EUD and highest minimum dose in the CTV under condition of a constant NTCP of the lungs. We conclude that the concept of homogeneous dose in the target volume is not the best approach to reach the highest probability of tumor control for lung tumors.

Role of Inhibition in Cortical Reorganization of the Adult Raccoon Revealed by Microiontophoretic Blockade of GABAAReceptors

Cortical reorganization was induced by amputation of the 4th digit in 11 adult raccoons. Animals were studied at various intervals, ranging from 2 to 37 wk, after amputation. Recordings were made from a total of 129 neurons in the deafferented cortical region using multibarrel micropipettes. Several types of receptive fields were described in reorganized cortex: restricted fields were similar in size to the normal receptive fields in nonamputated animals; multi-regional fields included sensitive regions on both adjacent digits and/or the underlying palm and were either continuous over the entire field or consisted of split fields. The proportion of neurons with restricted fields increased with time after amputation and was greater than previously found in subcortical regions. A GABA(A) receptor antagonist (bicuculline methiodide), glutamate, and GABA were administered iontophoretically to these neurons while determining their receptive fields and thresholds. Bicuculline administration resulted in expansion of the receptive field in 60% of the 93 neurons with cutaneous fields. In most cases (33 neurons) this consisted of a simple expansion around the borders of the predrug receptive field, and the average expansion (426%) was not different from that seen in nonamputated animals. In some neurons (n = 4), bicuculline produced an expansion from one digit onto the adjacent palm or another digit, an effect never seen in control animals. Bicuculline also changed the split fields of seven neurons into continuous fields by exposing a responsive region between the split fields. Finally, bicuculline changed the internal receptive field organization of 10 neurons by revealing subfields with reduced thresholds. In contrast to the situation in nonamputated animals, iontophoretic administration of glutamate also produced receptive field expansion in some neurons (n = 6), but the size and/or shape of the change was different from that produced by bicuculline, indicating that the effects of bicuculline were not due to an overall facilitation of neuronal activity. These results are consistent with the hypotheses that an important component of long-term cortical reorganization is the gradual reduction in effective receptive field size and that intracortical inhibitory networks are partially responsible for these changes.

Beam intensity modulation to reduce the field sizes for conformal irradiation of lung tumors: a dosimetric study

Purpose: In conformal radiotherapy of lung tumors, penumbra broadening in lung tissue necessitates the use of larger field sizes to achieve the same target coverage as in a homogeneous environment. In an idealized model configuration, some fundamental aspects of field size reduction were investigated, both for the static situation and for a moving tumor, while maintaining the dose homogeneity in the target volume by employing a simple beam-intensity modulation technique.Methods and Materials: An inhomogeneous phantom, consisting of polystyrene, cork, and polystyrene layers, with a 6 × 6 × 6 cm3 polystyrene cube inside the cork representing the tumor, was used to simulate a lung cancer treatment. Film dosimetry experiments were performed for an AP-PA irradiation technique with 8-MV or 18-MV beams. Dose distributions were compared for large square fields, small square fields, and intensity-modulated fields in which additional segments increase the dose at the edge of the field. The effect of target motion was studied by measuring the dose distribution for the solid cube, displaced with respect to the beams.Results: For the 18-MV beam, the field sizes required to establish a sufficient target coverage are larger than for the 8-MV beam. For each beam energy, the mean dose in cork can significantly be reduced (at least a factor of 1.6) by decreasing the field size with 2 cm, while keeping the mean target dose constant. Target dose inhomogeneity for these smaller fields is limited if the additional edge segments are applied for 8% of the number of monitor units given with the open fields. The target dose distribution averaged over a motion cycle is hardly affected if the target edge does not approach the field edge to within 3 mm.Conclusions: For lung cancer treatment, a beam energy of 8 MV is more suitable than 18 MV. The mean lung dose can be significantly reduced by decreasing the field sizes of conformal fields. The smaller fields result in the same biological effect to the tumor if the mean target dose is kept constant. Intensity modulation can be employed to maintain the same target dose homogeneity for these smaller fields. As long as the target (with a 3 mm margin) stays within the field portal, application of a margin for target motion is not necessary.

Spatio-temporal receptive fields in carp retinal horizontal cells.

1. The dynamics of the receptive fields of retinal horizontal cells were examined by applying a spatio-temporal modulated light signal to the retina. 2. The spatio-temporal receptive fields of both cone- and rod-driven horizontal cells, estimated through cross-correlation between the modulated light signal and the cells' responses, showed their receptive fields (the space-dependent component) to be reduced in size with time. 3. In cone-driven horizontal cells, the reduction in receptive field size was initially small but then rapidly became prominent with time. The time to peak of the time-dependent component of spatio-temporal receptive fields did not depend on the distance from the centre. 4. Application of a small amount of Co2+, an agent blocking the cone-driven horizontal cells' feedback action on cones, or GABA, resulted in a reversal of the time-dependent shrinkage of receptive fields to time-dependent expansion. 5. In rod-driven horizontal cells, the receptive field shrinkage was slow. The time to peak of the time-dependent component decreased with the distance from the centre. 6. Image processing experiments examining the response pattern in the horizontal cell layer (neural image) to a moving square of light showed smudging of the neural image when the time-dependent receptive field expansion was present, while there was essentially no smudging under conditions of receptive field shrinkage.

GLYCINE RECEPTORS ARE INVOLVED IN ANESTHETIC EFFECTS OF HALOTHANE ON SPINAL DORSAL HORN LOW-THRESHOLD NEURONS IN THE RAT

S471 INTRODUCTION: We have been studying a series of effects of anesthetics on spinal dorsal horn neurons. These suggest that reduction in low-threshold receptive field (RF) size, which is induced by inhalation anesthetics, is in part mediated by GABAA receptors, and that other transmitter systems are possibly responsible for the additional effect. In the CNS the major inhibitory neurotransmitters are thought to be GABA and glycine: GABA is predominant in the brain and glycine predominates in the spinal cord [1]. Thus, glycine receptors may be involved in anesthetic action of halothane within the spinal cord. The present study was designed to examine the effects of the glycine receptor antagonist strychnine on halothane-induced reduction of low-threshold RF size. METHODS: This protocol was approved by our institutional Animal Care and Use Committee. Extracellular activity of single spinal dorsal horn neurons was recorded in spinal cord-transected and decerebrated Sprague-Dawley rats (320-450g). Arterial blood pressure and end-tidal CO2 were monitored throughout the experiment. The low-threshold RF size was mapped in the unanesthetized state and in the presence of 1.1% (1 MAC) halothane. Animals then received i.v. strychnine to a cumulative dose of 2.0 mg/kg. Statistical significance was assessed by ANOVA and Bonferroni test with P value < 0.05 considered significant. RESULTS: In the absence of halothane, cumulative doses up to 2.0 mg/kg of strychnine did not affect RF size (107 +/- 10% of control, n=7), but it produced a significant partial, but not complete, reversal of halothane-induced reduction of the low-threshold RF size in a dose-related manner (Figure 1, n=8).Figure 1CONCLUSIONS: These results suggest that halothane reduction of low-threshold RF size is due in part to interactions at glycine receptors. As we have shown with GABAA and serotonin, each of these inhibitors only partially alters the neuronal responses, suggesting a complex pharmacology rather than a unitary mechanism of action. Supported, in part, by NIH GM 44954.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.

Field margin reduction using intensity-modulated x-ray beams formed with a multileaf collimator

Purpose : In axial, coplanar treatments with multiple fields, the superior and inferior ends of a planning target volume (PTC) are at risk to get underdosed due to the overlapping penumbras of all treatment fields. We have investigated a technique using intensity modulated x-ray beams that allows the use of small margins for definition of the superior and inferior field borders while still reaching a minimum PTV-dose of 95% of the isocenter dose. Methods and Materials : The applied intensity modulated beams, generated with a multileaf collimator, include narrow (1.1-1.6 cm) boost fields to increase the dose in the superior and inferior ends of the PTV. The benefits of this technique have been assessed using 3D treatment plans for 10 prostate cancer patients. Treatment planning was performed with the Cadplan 3D planning system (Varian-Dosetek). Dose calculations for the narrow boost fields have been compared with measurements. The applications of the boost fields has been tested on the MM50 Racetrack Microtron (Scanditronix Medical AB), which allows fully computer-controlled setup of all involved treatment fields. Results : Compared to our standard technique, the superior-inferior field length can be reduced by 1.6 cm, generally yielding smaller volumes of rectum and bladder in the high dose region. For the narrow boost fields, calculated relative dose distributions agree within 2% or 0.2 cm with measured dose distributions. For accurate monitor unit calculations, the phantom scatter table used in the Cadplan system had to be modified using measured data for square fields smaller than 4 × 4 cm 2. The extra time needed at the MM50 for the setup and delivery of the boost fields in usually about 1 min. Conclusion : The proposed use of intensity modulated beams yields improved conformal dose distributions for treatment of prostate cancer patients with a superior-inferior field size reduction of 1.6 cm. Treatments of other tumor sites can also benefit from the application of the boost fields.

Ultrasound image fusion for external beam radiotherapy for prostate cancer

Purpose : To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determined (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real time imaging. Methods and Materials : During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique. Results : The transrectal ultrasound probe enabled real-time prostrate imaging. The lateral field size can be reduced to 6.08 × 5.68 cm 2 ± 0.62 × 0.48 cm 2 from the standard 8 × 8 cm 2 field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field in 1.75 cm 2 ± 0.85 cm 2. Conclusion : The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.

Active tactile exploration influences the functional maturation of the somatosensory system

1. The hypothesis that active exploration of objects is required for the functional maturation of neuronal circuits subserving tactile perception was tested by subjecting 8- to 11-day old rats to a complete unilateral section of the facial nerve. This procedure selectively abolished whisker protraction movements without affecting the sensory innervation of the facial vibrissae, the tactile organs used by rats to discriminate object texture and shape. 2. Six to 14 mo after the facial nerve section, simultaneous recordings of neuronal ensembles located in the ventral posterior medial nucleus (VPM) of the thalamus revealed a marked reduction in receptive field (RF) size (in terms of number of whiskers), and the formation of abnormal RF surrounds, spanning the face and contiguous body regions. In addition, the directional organization of VPM RFs, represented by caudal to rostral shifts in RF centers over 30 ms following whisker stimulation, was greatly reduced in these animals. 3. These results suggest that neonatal active tactile exploration is required to establish normal spatiotemporal patterning of neuronal RFs within the somatosensory system, and consequently, to develop normal tactile perception.

323Intensity modulation with an MLC for field size reduction in conformal radiotherapy

323Intensity modulation with an MLC for field size reduction in conformal radiotherapy

Halothane effects on low-threshold receptive field size of rat spinal dorsal horn neurons appear to be independent of supraspinal modulatory systems

Recent evidence strongly supports the importance of spinal sites of action for the ability of general anesthetic agents to block response to noxious stimuli. This study was designed to examine possible spinal anesthetic effects on non-noxiously evoked activity. Three groups of rats were prepared for acute experiments in which the response of spinal dorsal horn neurons to low threshold receptive field (RF) stimulation was evaluated. In each animal in each group extracellular activity was recorded from a single spinal dorsal horn neuron. A low-threshold RF of each neuron and, at times, the sensitivity to low-threshold stimulation of multiple sites in the RF were determined under baseline conditions (light anesthesia or decerebrate). In Group 1, reversible cooling of the thoracic spinal cord in the presence of either 0.5% or 1% halothane anesthesia caused no change in RF size. However, an increase from 0.5% to 1% halothane caused a 53% decrease in RF size both in the presence and absence of a reversible cold block of the spinal cord. In Group 2, animals with spinal cords transected at the thoracic level had a similar change in low-threshold receptive field size (52%) when halothane concentrations were increased from 0.5% to 1%. Testing sensitivity within the RF areas indicated that the silenced areas at the fringe of the receptive field could still elicit activation of spinal dorsal horn neurons but at a higher threshold. In the final group of animals, decerebration and spinal cord transection allowed us to compare effects of 0.5% and 1% halothane with an anesthetic free baseline. Here, again, a dose-dependent reduction in RF area was observed although the baseline RFs were significantly smaller than those in Groups 1 and 2. These results demonstrate that the reduction in low-threshold receptive field size due to the administration of the inhalation anesthetic halothane occurs in the absence of descending modulation from supraspinal sites. This implicates the spinal dorsal horn as a potentially important site of action for general anesthetics. These results also support the spinal cord as an important tool to study the pharmacology responsible for anesthetic effects on sensory processing.

Magnification factors, receptive field images and point-image size in the superior colliculus of flying foxes: comparison with the primary visual cortex

The magnification factor (MF) of the stratum griseum superficiale (SGS) of the superior colliculus (SC) was calculated based on visual receptive fields recorded from anaesthetised and paralysed flying foxes (Pteropus spp.). In areal terms, the MF at the representation of central vision was 4-6 times larger than that in the peripheral representation. This variation is less marked than that observed in the primary visual area (V1), but is roughly that expected if the retinotopic map in the SC was defined by the distribution of ganglion cells in the retina. Two measures of the functional spread of activity in the SC, the receptive field images and the point-image size, were calculated. Receptive field images are remarkably similar throughout the SC. As in V1, the point-image size in the SGS of flying foxes is 0.5-0.6 mm and varies little with eccentricity. Bilateral ablation of the visual cortex results in a reduction of the mean receptive field size of neurones in the SGS, and the point-image size is reduced by half. However, the shape of the point-image function is not affected. These results demonstrate that the spread of activity in the SC is nearly constant throughout the retinotopic map and that this is primarily a result of the direct retinal projection. Although the visual cortex has an expanded central representation in comparison with the SC, the corticotectal pathway does not exert a preferential influence on the central representation of the SC.

Hyperfractionated radiation therapy (hfx rt) followed by multiagent chemotherapy (CHT) in patients with malignant glioma: A phase II study

Purpose : Forty-eight patients with malignant glioma were treated with hyperfractionated radiation therapy followed by multiagent chemotherapy to explore feasibility and toxicity of such combined modality treatment. Methods and Materials : There were 34 males and 14 females with a median age of 53 years (range, 32–74 years) and median Eastern Cooperative Oncology Group performance status score of 1 (range, 0–3). Histology included anaplastic astrocytoma in 11 patients and glioblastoma multiforme in 37 patients. Radiation was given at 1.2 Gy per fraction, two fractions per day, for a total dose of 72 Gy, with a reduction in field size after 52.8 Gy. Four weeks after completion of hyperfractionated radiation therapy multiagent chemotherapy was introduced with bis-chlorethyl nitrosourea (BCNU) 50 mg/m 2, days 1–3, vincristine 1.4 mg/m 2 (max. 2 mg), day 1, procarbazine 50 mg/m 2, days 1–7 and cisplatin 20 mg/m 2, days 1–3. Cycles were repeated every 4 weeks to a maximum of six cycles or until tumor progression was noted. Results : Median survival time for all patients was 52 weeks (range, 16–185 weeks) and median time to tumor progression was 30.5 weeks (range, 12–131 weeks). Besides age, histology, performance status, and extent of surgery, interfraction interval and location of tumor influenced survival in glioblastoma multiforms patients on univariate analysis: Patients treated with shorter intervals (4.5 – 5 h) did better than those treated with longer intervals (5.5–6 h); also, glioblastoma multiforme patients with frontal tumors did better than those with tumors of the other locations. Multivariate analysis confirmed that the performance status, interfraction interval, and tumor location were significant prognostic factors in glioblastoma multiforme patients. Acute toxicity was mild. No cases of brain necroses were observed. Conclusion : Hyperfractionated radiation therapy followed by multiagent chemotherapy was well tolerated with mild acute and virtually no late toxicity. More patients and longer follow-up are needed for further evaluation of its activity and late effects in anaplastic astrocytoma patients.

Small and large field grating acuity versus recognition acuity in different groups of amblyopic patients

Grating acuity was tested in 74 subjects with different amblyopia and five patients with pathological morphological findings, reducing visual acuity. Recognition acuity was tested with Landolt C single symbol and close inter-space 2.6 min. of arc. Grating acuity was tested with the Teller Acuity Cards with large (12.5 cm × 12.5 cm) and small (6.25 cm × 6.25 cm) test fields. Reduction of field size did not cause any significant difference. Patients with strabismic or strabismic and anisometropic amblyopia did not show a close correlation of recognition acuity with grating acuity. Stimulus deprivation amblyopia showed a good correlation between grating acuity (large and small field) and Landolt single optotype acuity. In children at risk for amblyopia, a difference in favour of large field gratings was found for both eyes (risk and non-risk eye) in the lower visual acuity group (identical with the lower age group). Better grating acuity for large fields seems to reflect an early stage of the visual development rather than that it is indicative for amblyopia.

Visual performance in behaving cats after prenatal unilateral enucleation.

Prenatal unilateral enucleation in mammals causes an extensive anatomical reorganization of visual pathways. The remaining eye innervates the entire extent of visual subcortical and cortical areas. Electrophysiological recordings have shown that the retino-geniculate connections are retinotopically organized and geniculate neurones have normal receptive field properties. In area 17 all neurons respond to stimulation of the remaining eye and retinotopy, orientation columns, and direction selectivity are maintained. The only detectable change is a reduction in receptive field size. Are these changes reflected in the visual behavior? We studied visual performance in cats unilaterally enucleated 3 weeks before birth (gestational age at enucleation, 39-42 days). We tested behaviorally the development of visual acuity and, in the adult, the extension of the visual field and the contrast sensitivity. We found no difference between prenatal monocularly enucleated cats and controls in their ability to orient to targets in different positions of the visual field or in their visual acuity (at any age). The major difference between enucleated and control animals was in contrast sensitivity:prenatal enucleated cats present a loss in sensitivity for gratings of low spatial frequency (below 0.5 cycle per degree) as well as a slight increase in sensitivity at middle frequencies. We conclude that prenatal unilateral enucleation causes a selective change in the spatial performance of the remaining eye. We suggest that this change is the result of a reduction in the number of neurones with large receptive fields, possibly due to a severe impairment of the Y system.

Activation of Protein Kinase C Modulates Light Responses in Horizontal Cells of the Turtle Retina.

The effect of phorbol esters on the light-evoked responses of horizontal cells were studied in the turtle eyecup preparation. Phorbol esters caused a reduction in receptive field size and a significant decrease in the amplitude of responses to annular and full-field illumination; however, they caused only minor changes in responses to small spots in the receptive field centre. The dark membrane potential was not affected. The results suggest that phorbol esters may affect both coupling resistance and membrane resistance in horizontal cells. The effects of phorbol esters were blocked by the protein kinase C inhibitor staurosporine, and inactive phorbol ester had no effect, making it very likely that the phorbol ester effects were mediated through activation of protein kinase C. The above effects of the phorbol esters were considerably reduced by the dopamine antagonists haloperidol and fluphenazine, suggesting that they were in part mediated by release of dopamine.

Dosimetry of Small Field Electron Beams

Measurements of the central axis depth dose curves, isodose profiles and field size dependence of the output factors for small field electron beams from a Varian Clinac 18 linear accelerator have been performed. Energies of electron beams studied were 6, 9, 12, 15, and 18 MeV. Circular fields of 1, 2, 3, 5, and 8 cm diameter were obtained from cerrobend shields attached to the bottom face of a 15 × 15 cm2 electron cone applicator. Measurements were carried out in a water phantom with an ionization chamber and a silicon diode detector and in a polystyrene phantom with Kodak XV-2 film. For all energies studied, as the field size of the electron beam becomes smaller: (1) the depth of maximum dose shifts toward the surface, (2) the depth of 90% and 80% dose, which are common dose prescription depths, becomes smaller, (3) the surface dose increases, and (4) the dose fall-off region becomes more gradual. The output of the electron beam reduces significantly with reduction in electron beam field size as a consequence of lack of lateral equilibrium. Hence, for accurate treatment planning for small electron fields, it is essential that the beam characteristics be individually measured.

High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas

A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment — both healing spontaneously. Fourteen patients developed an area of moist desquamation — 11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none. There has been one local failure associated with regional node involvement and lung metastases. Although it was feasible to deliver the planned very high doses to these patients by the use of hyperfractionation, early results suggest that the late damage caused by this regime is greater than that from standard once daily 2 Gy fractionation to a total dose of 60 Gy in 6 weeks. A lower dose per fraction is now being evaluated.

Thermal-field-emission electron optics for nanolithography

A new column design for the 25-kV vector-scan Gaussian beam lithography system is described. A field-emission gun, consisting of a three-element electrostatic lens and Zr/O/W〈100〉 cathode operated in a thermal-field mode for current stability, is combined in a demagnifying optics with a magnetic objective lens to focus a high-current-density (1000–3000 A/cm2) electron beam at high resolution (100–300 Å) at the wafer plane without a severe reduction in field size. Optimum beam semiangle, focus mode, and column magnification are determined. The modified system retains the original deflection coils and pattern-generation system which allows immediate implementation of existing subfield stitching, chip registration, and proximity correction software.

The determination of aldehyde oxidase activity patterns in the wing discs of Drosophila melanogaster : Absence of field size influence during the third larval instar.

The pattern of aldehyde oxidase (AO) activity was determined in wing discs of Drosophila melanogaster larvae homozygous for the mutants apt 73n, Beaded, and vestigial (vg) in order to determine if reduction in field size in the pouch could be related to alterations of the wild-type AO pattern, as suggested by the Kauffman (1978) hypothesis. The pattern in wild-type discs was resolved into six areas for comparison with mutant discs. vg discs developed at 25° C showed restriction of the pattern into a small area on the anterior side of the disc, and comparison of vg and wild-type prepupal wings allowed positive identification of the AO pattern elements which remained. AO patterns in vg wing discs grown at 27°, 29°, and 31° C were progressively more complete and similar to wild-type, reflecting the reduction in cell death in discs grown at higher temperatures. These results show that cell loss during the third instar in vg development at 25° C is responsible for the alteration of the AO pattern, rather than field size reduction, and that determination of the pattern must take place much earlier than the time of its first appearance during the third larval instar, and before cell death in vg discs begins. Thus mutants acting at earlier stages will be necessary for further tests of the Kauffman hypothesis.